Schizophrenia researchers continue to seek evidence for a disturbance of neurodevelopment in schizophrenia. To precisely determine the characteristics of neuroanatomical abnormalities in schizophrenia, i.e., volume loss, exaggerated or reversed asymmetries, and shape deformations) would provide critical evidence for evaluating this neurodevelopmental hypothesis. In addition, similar neuroanatomical abnormalities among several limbic-cortical structures would suggest a disturbance within this particular neurocircuit in schizophrenia. However, to precisely define neuroanatomical abnormalities, improved methodologies for neuromorphometry are needed. Current manual and semi-automated methods for neuromorphometry provide only volume measurements and substantial human effort is required to avoid measurement errors. Methods to study brain structure asymmetries and shape are even less well available. The investigator and his colleagues have developed automated methods for neuromorphometry, using high dimensional transformations of a neuroanatomical template to map target MR scans. The investigator has shown that these methods can be used to measure hippocampal volumes with greater reliability than manual outlining, and that they can be used to conduct a precise analysis of hippocampal shape, which discriminates schizophrenia and control subjects with greater power than volume comparison. He now proposes to further develop these methods by adding information about other brain structures to the neuroanatomical template, and then testing a set of hypotheses regarding volume, symmetry and shape in larger groups of subjects. The specific aims of this project are to: 1) measure and compare limbic-cortical volumes on MR scans in schizophrenia and control subjects by applying high dimensional transformations of a neuroanatomical template, 2) quantify and compare interhemispheric asymmetries in schizophrenia and control subjects by applying high dimensional inversion transformations within each subject, 3) construct composite limbic-cortical shapes in schizophrenia and control subjects and compare these shapes by using the linear combination of optimal shape eigenvectors, and 4) assess the schizophrenia subjects for onset of illness, duration of illness, severity of three symptom groupings, and then to test hypotheses regarding relationships between these clinical variables and volume, symmetry, and shape measures.